Diabetic osteopathy, one of the complications of long-standing, poorly controlled diabetes, leads to diminished bone formation, retardation of bone healing, and osteoporosis. Bone mineral density (BMD) and biomechanical integrity are referential predictors of fracture, and patients with type 1 diabetes incur a higher incidence of fractures compared to healthy individuals. Therefore, BMD and histomorphometry were used to evaluate the potential of drugs to prevent the osteopenia associated with type diabetes (Bain S, et al., Bone, 1997; 21(2):147-153; Suzuki K, et al., Bone, 2003; 33(1):108-114). The structural integrity of the femur or tibia was also examined in order to evaluate the biomechanical consequences of diabetes (Reddy G K, et al., Diabetes Res. Clin. Pract., 2001; 54(1):1-8).
In recent years, the potential use of vanadium as an alternative or adjunct treatment for glycemic control of diabetes has been examined (Poucheret P, et al., Mol. Cell. Biochem., 1998; 188(1-2):73-80). For example, vanadyl acetylacetonate (also called bis(acetylacetonate)oxovanadium(IV), VO(acac)2, or VAC) has demonstrated insulin-mimetic effects in studies of type 1 and type 2 diabetic animals (e.g. Crans D C, J. Inorg. Biochem., 2000; 80(1-2):123-131) and humans (e.g., Goldfine A B, et al., Mol. Cell. Biochem., 1995; 153(1-2):217-231) and prevented some of the associated complications of diabetes in animal studies (e.g., Bhanot S, et al., Mol. Cell. Biochem., 1995; 153(1-2):205-209). Additional pharmacological activities of VAC studied include the inhibition of gluconeogenesis (Kiersztan A, Biochem. Pharmacol., 2002; 63(7):1371-1382), a decrease in glutamate dehydrogenase activity (Kiersztan A, et al., Pharmacol. Toxicol. 1998; 82(4):167-172), and antilipolysis (Li J, et al., Endocrinology, 1997; 138(6):2274-2279).
Several studies have demonstrated VAC improved the ultimate strength, Tb,Th, MAR, and plasma osteocalcin in diabetic rats; however, VAC did not affect any bone parameters in normal rats in this non-injury and non fracture model of bone homeostasis (Facchini D M, et al., Bone, 2006; 38(3):368-377; Zhang S Q, et al., J. Bone Miner. Metab., 2007; 25(5):293-301). The results from an in vitro model using osteoblast-like cells showed that vanadium exerted biphasic effects: a low concentration of vanadium stimulated osteoblast proliferation and differentiation, but a high concentration inhibited these effects (Bain S, et al., Bone, 1997; 21(2):147-153; Cortizo A M, et al., Toxicology, 2000; 147(2):89-99; Cortizo A M, et al., Eur. J. Pharmacol., 2000; 400(2-3):279-285; Cortizo A M and Etcheverry S B, Mol. Cell. Biochem., 1995; 145(2):97-102; Suzuki K, et al., Bone, 2003; 33(1):108-114). In vivo studies indicate that vanadium therapy can improve bone quality in diabetic animal models (Facchini D M, et al., Bone, 2006; 38(3):368-377; Zhang S Q, et al., J. Bone Miner. Metab. 2007; 25(5):293-301). However, in vivo evaluation data on bone fracture healing in the presence of vanadium are still unavailable, and no evaluation of vanadium composite as a surface coating on orthopedic devices for bone fracture healing or other bone regenerative processes has been performed.